2023
Multiscale genetic architecture of donor-recipient differences reveals intronic LIMS1 mismatches associated with kidney transplant survival
Sun Z, Zhang Z, Banu K, Gibson I, Colvin R, Yi Z, Zhang W, De Kumar B, Reghuvaran A, Pell J, Manes T, Djamali A, Gallon L, O'Connell P, He J, Pober J, Heeger P, Menon M. Multiscale genetic architecture of donor-recipient differences reveals intronic LIMS1 mismatches associated with kidney transplant survival. Journal Of Clinical Investigation 2023, 133: e170420. PMID: 37676733, PMCID: PMC10617779, DOI: 10.1172/jci170420.Peer-Reviewed Original ResearchConceptsDeath-censored graft lossHuman leukocyte antigenExpression quantitative trait lociT cellsTGF-β1TGF-β1/Smad pathwayDonor-recipient differencesKidney allograft lossChronic allograft rejectionKidney transplant survivalDonor-recipient mismatchActive TGF-β1Allograft lossGraft lossAllograft rejectionTransplant cohortPeripheral bloodLeukocyte antigenClinical trialsImmune cellsHaplotype mismatchGenome-wide scaleTransplant survivalQuantitative trait lociSingle nucleotide polymorphism dataNonpodocyte Roles of APOL1 Variants: An Evolving Paradigm
Pell J, Nagata S, Menon M. Nonpodocyte Roles of APOL1 Variants: An Evolving Paradigm. Kidney360 2023, 4: e1325-e1331. PMID: 37461136, PMCID: PMC10550003, DOI: 10.34067/kid.0000000000000216.Peer-Reviewed Original ResearchConceptsApolipoprotein L1Progressive renal failureAPOL1 risk variantsImmune response genesParadigm of diseasesMechanisms of diseaseRenal failureKidney diseaseBody of evidenceImmune cellsClinical dataRecent African ancestryRisk genotypesAPOL1 variantsDiseaseEndothelial cellsPutative signaling pathwaysGenetic factorsSeminal dataPhenotype progressionCausal rolePodocytesRisk variantsSignaling pathwaysEvolving ParadigmHCK induces macrophage activation to promote renal inflammation and fibrosis via suppression of autophagy
Chen M, Menon M, Wang W, Fu J, Yi Z, Sun Z, Liu J, Li Z, Mou L, Banu K, Lee S, Dai Y, Anandakrishnan N, Azeloglu E, Lee K, Zhang W, Das B, He J, Wei C. HCK induces macrophage activation to promote renal inflammation and fibrosis via suppression of autophagy. Nature Communications 2023, 14: 4297. PMID: 37463911, PMCID: PMC10354075, DOI: 10.1038/s41467-023-40086-3.Peer-Reviewed Original ResearchConceptsChronic kidney diseasePro-inflammatory polarizationBone marrow-derived macrophagesRenal inflammationKidney fibrosisMacrophage activationHematopoietic cell kinaseMacrophage pro-inflammatory activityProgressive chronic kidney diseaseIschemia-reperfusion injury modelUnilateral ureteral obstruction kidneysChronic allograft injuryReperfusion injury modelPro-inflammatory activityPro-inflammatory macrophagesHck inhibitorsMarrow-derived macrophagesSuppression of autophagyAllograft injuryUUO miceRenal fibrosisKidney diseaseDiseased kidneysMacrophage numbersInjury modelAllograft tissue under the microscope: only the beginning
Virmani S, Rao A, Menon M. Allograft tissue under the microscope: only the beginning. Current Opinion In Organ Transplantation 2023, 28: 126-132. PMID: 36787238, PMCID: PMC10214011, DOI: 10.1097/mot.0000000000001052.Peer-Reviewed Original ResearchConceptsAllograft tissueArtificial intelligenceBanff schemaMachine learningDigital pathologyKidney allograft biopsiesApplication of AINovel molecular diagnosticsAllograft healthAllograft histologyAllograft biopsiesPathologic diagnosisImmunological activationTissue injuryHistopathological analysisClinical careTissue pathologyML algorithmsClinical useOrdinal outputsNovel modalityVivo microscopyPathologyBiopsyTissue
2022
Blood Transcriptomes of SARS-CoV-2–Infected Kidney Transplant Recipients Associated with Immune Insufficiency Proportionate to Severity
Sun Z, Zhang Z, Banu K, Al Azzi Y, Reghuvaran A, Fredericks S, Planoutene M, Hartzell S, Kim Y, Pell J, Tietjen G, Asch W, Kulkarni S, Formica R, Rana M, Maltzman JS, Zhang W, Akalin E, Heeger PS, Cravedi P, Menon MC. Blood Transcriptomes of SARS-CoV-2–Infected Kidney Transplant Recipients Associated with Immune Insufficiency Proportionate to Severity. Journal Of The American Society Of Nephrology 2022, 33: 2108-2122. PMID: 36041788, PMCID: PMC9678030, DOI: 10.1681/asn.2022010125.Peer-Reviewed Original ResearchConceptsKidney transplant recipientsImmune activation pathwaysImmunosuppressant useKTR cohortAcute illnessBlood transcriptomeAcute casesT cellsCOVID-19Most kidney transplant recipientsPost-acute COVID-19Adaptive immune system activationManagement of immunosuppressionReinstitution of immunosuppressionAcute COVID-19Serum inflammatory cytokinesCOVID-19 severity scoreCOVID-19 infectionImmune system activationUpregulation of neutrophilActivation pathwayTransplant recipientsChart reviewImmune signaturesLymphocyte countInfliximab Induction Lacks Efficacy and Increases BK Virus Infection in Deceased Donor Kidney Transplant Recipients: Results of the CTOT-19 Trial
Hricik D, Armstrong B, Alhamad T, Brennan D, Bromberg J, Bunnapradist S, Chandran S, Fairchild R, Foley D, Formica R, Gibson I, Kesler K, Kim SJ, Mannon R, Menon M, Newell K, Nickerson P, Odim J, Poggio E, Sung R, Shapiro R, Tinckam K, Vincenti F, Heeger P. Infliximab Induction Lacks Efficacy and Increases BK Virus Infection in Deceased Donor Kidney Transplant Recipients: Results of the CTOT-19 Trial. Journal Of The American Society Of Nephrology 2022, 34: 145-159. PMID: 36195441, PMCID: PMC10101585, DOI: 10.1681/asn.2022040454.Peer-Reviewed Original ResearchConceptsBiopsy-proven acute rejectionBK virus infectionIntravenous infliximabPrimary end pointTransplant recipientsKidney transplantVirus infectionDe novo donor-specific antibodiesDeceased donor kidney transplant recipientsRabbit anti-thymocyte globulin (rATG) inductionAnti-thymocyte globulin inductionCLINICAL TRIAL REGISTRY NAMEDonor kidney transplant recipientsNovo donor-specific antibodiesEnd pointPhase 2 clinical trialIFX induction therapyTRIAL REGISTRY NAMEDelayed graft functionDonor-specific antibodiesKidney transplant recipientsDeceased donor kidneysTNF-α productionPrimary transplant recipientsAcute rejectionDonor–Recipient Non-HLA Variants, Mismatches and Renal Allograft Outcomes: Evolving Paradigms
Jethwani P, Rao A, Bow L, Menon MC. Donor–Recipient Non-HLA Variants, Mismatches and Renal Allograft Outcomes: Evolving Paradigms. Frontiers In Immunology 2022, 13: 822353. PMID: 35432337, PMCID: PMC9012490, DOI: 10.3389/fimmu.2022.822353.Peer-Reviewed Original ResearchConceptsAllograft outcomesImportant recent dataRenal allograft outcomeAcute allograft rejectionKidney allograft outcomesDonor-recipient mismatchRecipient's immune systemNatural history studiesNon-HLA lociMajority of casesOrgan allocation processPolymorphic HLA genesAcute rejectionAllograft longevityAllograft lossMaintenance immunosuppressionTransplant outcomesAllograft rejectionImmune mechanismsPatient deathRecipient pairsDonor organsHLA variantsImmune systemOvert evidence
2021
Recipient APOL1 risk alleles associate with death-censored renal allograft survival and rejection episodes
Zhang Z, Sun Z, Fu J, Lin Q, Banu K, Chauhan K, Planoutene M, Wei C, Salem F, Yi Z, Liu R, Cravedi P, Cheng H, Hao K, O’Connell P, Ishibe S, Zhang W, Coca SG, Gibson IW, Colvin RB, He J, Heeger PS, Murphy B, Menon MC. Recipient APOL1 risk alleles associate with death-censored renal allograft survival and rejection episodes. Journal Of Clinical Investigation 2021, 131 PMID: 34499625, PMCID: PMC8592534, DOI: 10.1172/jci146643.Peer-Reviewed Original ResearchConceptsDeath-censored allograft lossAPOL1 risk allelesRisk allelesTransplant outcomesDeath-censored renal allograft survivalRenal allograft survivalChronic allograft rejectionKidney transplant waitlistKidney transplant cohortRisk allele carriersAllograft lossAllograft survivalGraft lossRejection episodesTransplant cohortAllograft rejectionDonor kidneysNative kidneysNK cellsImmunomodulatory roleTransplant waitlistAPOL1 genotypeClinical trialsHealthy controlsHispanic recipientsDeep learning identified pathological abnormalities predictive of graft loss in kidney transplant biopsies
Yi Z, Salem F, Menon MC, Keung K, Xi C, Hultin S, Haroon Al Rasheed MR, Li L, Su F, Sun Z, Wei C, Huang W, Fredericks S, Lin Q, Banu K, Wong G, Rogers NM, Farouk S, Cravedi P, Shingde M, Smith RN, Rosales IA, O'Connell PJ, Colvin RB, Murphy B, Zhang W. Deep learning identified pathological abnormalities predictive of graft loss in kidney transplant biopsies. Kidney International 2021, 101: 288-298. PMID: 34757124, PMCID: PMC10285669, DOI: 10.1016/j.kint.2021.09.028.Peer-Reviewed Original ResearchConceptsGraft lossTransplant biopsiesDamage scoreBanff scoresPathological lesionsOne-year graft lossPost-transplant graft lossGlomerular filtration rate declineIntermediate-risk groupKidney allograft failurePost-transplant biopsiesKidney transplant biopsiesMononuclear leukocyte infiltrationTissue compartmentsMononuclear leukocyte infiltrateProtocol biopsiesAllograft failureTransplant recipientsClinical predictorsTubular atrophyGraft damageRisk stratificationInterstitial fibrosisLeukocyte infiltrationLeukocyte infiltrateAMP-Kinase mediates regulation of glomerular volume and podocyte survival
Banu K, Lin Q, Basgen JM, Planoutene M, Wei C, Reghuvaran AC, Tian X, Shi H, Garzon F, Garzia A, Chun N, Cumpelik A, Santeusanio AD, Zhang W, Das B, Salem F, LI L, Ishibe S, Cantley LG, Kaufman L, Lemley KV, Ni Z, He JC, Murphy B, Menon MC. AMP-Kinase mediates regulation of glomerular volume and podocyte survival. JCI Insight 2021, 6: e150004. PMID: 34473647, PMCID: PMC8525649, DOI: 10.1172/jci.insight.150004.Peer-Reviewed Original ResearchAdenylate KinaseAdolescentAdultAgedAlbuminuriaAnimalsCell SizeCell SurvivalChildChild, PreschoolFemaleGene Knockdown TechniquesGlomerulonephritis, MembranousGlomerulosclerosis, Focal SegmentalHumansHypertrophyInfantKidney GlomerulusMaleMiceMicrofilament ProteinsMiddle AgedNephrectomyNephrosis, LipoidNephrotic SyndromePodocytesProportional Hazards ModelsProto-Oncogene Proteins c-fynYoung Adult
2020
Magnetic resonance elastography vs. point shear wave ultrasound elastography for the assessment of renal allograft dysfunction
Kennedy P, Bane O, Hectors SJ, Gordic S, Berger M, Delaney V, Salem F, Lewis S, Menon M, Taouli B. Magnetic resonance elastography vs. point shear wave ultrasound elastography for the assessment of renal allograft dysfunction. European Journal Of Radiology 2020, 130: 109180. PMID: 32736305, DOI: 10.1016/j.ejrad.2020.109180.Peer-Reviewed Original ResearchGenome-wide non-HLA donor-recipient genetic differences influence renal allograft survival via early allograft fibrosis
Zhang Z, Menon MC, Zhang W, Stahl E, Loza BL, Rosales IA, Yi Z, Banu K, Garzon F, Sun Z, Wei C, Huang W, Lin Q, Israni A, Keating BJ, Colvin RB, Hao K, Murphy B. Genome-wide non-HLA donor-recipient genetic differences influence renal allograft survival via early allograft fibrosis. Kidney International 2020, 98: 758-768. PMID: 32454123, PMCID: PMC7483801, DOI: 10.1016/j.kint.2020.04.039.Peer-Reviewed Original ResearchConceptsAllograft survivalIntimal fibrosisDeath-censored allograft survivalLong-term allograft failureAcute rejection episodesDonor-recipient differencesRenal allograft survivalHuman leukocyte antigen (HLA) lociNon-HLA SNPsLong-term survivalAllograft failureHLA mismatchesKidney recipientsRejection episodesSubclinical rejectionAllograft fibrosisMultivariable analysisHistologic damageR differencesOrgan SharingCox modelFibrosisHLA regionSurvivalGenome-wide single-nucleotide polymorphism array data
2019
Multiparametric magnetic resonance imaging shows promising results to assess renal transplant dysfunction with fibrosis
Bane O, Hectors S, Gordic S, Kennedy P, Wagner M, Weiss A, Khaim R, Yi Z, Zhang W, Delaney V, Salem F, He C, Menon MC, Lewis S, Taouli B. Multiparametric magnetic resonance imaging shows promising results to assess renal transplant dysfunction with fibrosis. Kidney International 2019, 97: 414-420. PMID: 31874802, PMCID: PMC6983343, DOI: 10.1016/j.kint.2019.09.030.Peer-Reviewed Original ResearchConceptsCortical apparent diffusion coefficientApparent diffusion coefficientChronic dysfunctionMedullary apparent diffusion coefficientsProspective single-center studyFractional anisotropyMultiparametric magnetic resonance imagingRenal allograft histologyRenal transplant dysfunctionTubular atrophy scoreRenal allograft dysfunctionRenal transplant patientsSingle-center studyMagnetic resonance imaging protocolIntravoxel incoherent motion diffusion-weighted imagingNon-invasive assessmentTest-retest repeatabilityMagnetic resonance imagingDiffusion-weighted imagingBlood oxygen levelDiffusion tensor imagingInter-observer reproducibilityAllograft dysfunctionAllograft histologyEGFR declineA Peripheral Blood Gene Expression Signature to Diagnose Subclinical Acute Rejection
Zhang W, Yi Z, Keung KL, Shang H, Wei C, Cravedi P, Sun Z, Xi C, Woytovich C, Farouk S, Huang W, Banu K, Gallon L, Magee CN, Najafian N, Samaniego M, Djamali A, Alexander SI, Rosales IA, Smith RN, Xiang J, Lerut E, Kuypers D, Naesens M, O'Connell PJ, Colvin R, Menon MC, Murphy B. A Peripheral Blood Gene Expression Signature to Diagnose Subclinical Acute Rejection. Journal Of The American Society Of Nephrology 2019, 30: 1481-1494. PMID: 31278196, PMCID: PMC6683710, DOI: 10.1681/asn.2018111098.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBiomarkersBiopsyFemaleGene Expression ProfilingGenomicsGraft RejectionGraft SurvivalHumansImmunosuppressive AgentsInflammationKaplan-Meier EstimateKidney Failure, ChronicKidney TransplantationMaleMiddle AgedOligonucleotide Array Sequence AnalysisProspective StudiesRisk FactorsSequence Analysis, RNAConceptsSubclinical acute rejectionKidney transplant recipientsAcute cellular rejectionAcute rejectionTransplant recipientsSurveillance biopsiesACR 3Graft functionHigh riskIndependent cohortPeripheral blood gene expression signaturesClinical acute rejectionFuture graft lossOngoing acute rejectionStable graft functionBlood gene expression signaturesCellular rejectionGraft lossGraft outcomeGraft survivalBorderline changesGene expression signaturesCox analysisHistologic featuresPeripheral blood
2018
SHROOM3-FYN Interaction Regulates Nephrin Phosphorylation and Affects Albuminuria in Allografts
Wei C, Banu K, Garzon F, Basgen JM, Philippe N, Yi Z, Liu R, Choudhuri J, Fribourg M, Liu T, Cumpelik A, Wong J, Khan M, Das B, Keung K, Salem F, Campbell KN, Kaufman L, Cravedi P, Zhang W, O'Connell PJ, He JC, Murphy B, Menon MC. SHROOM3-FYN Interaction Regulates Nephrin Phosphorylation and Affects Albuminuria in Allografts. Journal Of The American Society Of Nephrology 2018, 29: 2641-2657. PMID: 30341149, PMCID: PMC6218856, DOI: 10.1681/asn.2018060573.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonAdolescentAdultAgedAlbuminuriaAllograftsAnimalsChildChild, PreschoolEnhancer Elements, GeneticFemaleGene Knockdown TechniquesGlomerular Filtration RateHomozygoteHumansKidneyKidney TransplantationMaleMembrane ProteinsMiceMice, 129 StrainMice, Inbred C57BLMice, KnockoutMicrofilament ProteinsMiddle AgedPhosphorylationPodocytesPolymorphism, Single NucleotideProto-Oncogene Proteins c-fynRenal Insufficiency, ChronicRNA, Small InterferingSignal TransductionSrc Homology DomainsYoung AdultConceptsDiffuse foot process effacementKnockdown miceFoot process effacementReduced albuminuriaAllograft fibrosisRenal functionDonor kidneysLower GFRRenal fibrosisTGF-b signalingHuman allograftsNephroseq databaseBiopsy samplesProcess effacementProtective roleAlbuminuriaAdult glomeruliHuman podocytesKnockdown podocytesCKDHuman dataPodocytesAllograftsActin cytoskeleton pathwayFibrosis
2017
Analysis of OPTN/UNOS registry suggests the number of HLA matches and not mismatches is a stronger independent predictor of kidney transplant survival
Yacoub R, Nadkarni GN, Cravedi P, He JC, Delaney VB, Kent R, Chauhan KN, Coca SG, Florman SS, Heeger PS, Murphy B, Menon MC. Analysis of OPTN/UNOS registry suggests the number of HLA matches and not mismatches is a stronger independent predictor of kidney transplant survival. Kidney International 2017, 93: 482-490. PMID: 28965746, DOI: 10.1016/j.kint.2017.07.016.Peer-Reviewed Original ResearchMeSH KeywordsDelayed Graft FunctionGraft RejectionGraft SurvivalHistocompatibilityHistocompatibility TestingHLA AntigensHumansKidney TransplantationPredictive Value of TestsProtective FactorsRegistriesRetrospective StudiesRisk FactorsTime FactorsTissue and Organ ProcurementTreatment OutcomeUnited StatesConceptsDelayed graft functionGraft survivalHLA matchingGraft functionDeceased donor kidney transplant patientsDeceased donor kidney transplant recipientsOne-year acute rejection ratesDeath-censored graft survivalOne-year acute rejectionOPTN/UNOS registryDonor kidney transplant recipientsAcute rejection ratesKidney transplant patientsKidney transplant recipientsOrgan Sharing databaseKidney transplant survivalDegree of HLAStrong independent predictorUNOS registryAcute rejectionGraft outcomeTransplant recipientsTransplant patientsHLA matchIndependent predictorsAPOL1 G2 risk allele—clarifying nomenclature
Zhang Z, Hao K, Ross MJ, Murphy B, Menon MC. APOL1 G2 risk allele—clarifying nomenclature. Kidney International 2017, 92: 518-519. PMID: 28709608, DOI: 10.1016/j.kint.2017.05.009.Peer-Reviewed Original Research
2016
Biopsy transcriptome expression profiling to identify kidney transplants at risk of chronic injury: a multicentre, prospective study
O'Connell PJ, Zhang W, Menon MC, Yi Z, Schröppel B, Gallon L, Luan Y, Rosales IA, Ge Y, Losic B, Xi C, Woytovich C, Keung KL, Wei C, Greene I, Overbey J, Bagiella E, Najafian N, Samaniego M, Djamali A, Alexander SI, Nankivell BJ, Chapman JR, Smith RN, Colvin R, Murphy B. Biopsy transcriptome expression profiling to identify kidney transplants at risk of chronic injury: a multicentre, prospective study. The Lancet 2016, 388: 983-993. PMID: 27452608, PMCID: PMC5014570, DOI: 10.1016/s0140-6736(16)30826-1.Peer-Reviewed Original ResearchConceptsChronic allograft damage indexAllograft lossKidney transplantPathological variablesChronic injuryEarly allograft lossKidney transplant recipientsRenal allograft recipientsFunction 3 monthsBaseline clinical variablesDevelopment of fibrosisAllograft recipientsNormal allograftsRenal allograftsTransplant recipientsAllograft fibrosisMulticentre studyProgressive injuryProspective studyClinical variablesIndependent cohortLower riskFibrosisPredictive valueTransplant
2014
Intronic locus determines SHROOM3 expression and potentiates renal allograft fibrosis
Menon MC, Chuang PY, Li Z, Wei C, Zhang W, Luan Y, Yi Z, Xiong H, Woytovich C, Greene I, Overbey J, Rosales I, Bagiella E, Chen R, Ma M, Li L, Ding W, Djamali A, Saminego M, O’Connell P, Gallon L, Colvin R, Schroppel B, He JC, Murphy B. Intronic locus determines SHROOM3 expression and potentiates renal allograft fibrosis. Journal Of Clinical Investigation 2014, 125: 208-221. PMID: 25437874, PMCID: PMC4382250, DOI: 10.1172/jci76902.Peer-Reviewed Original ResearchMeSH KeywordsAllograftsAnimalsBeta CateninDisease SusceptibilityEnhancer Elements, GeneticFibrosisGene ExpressionGenetic Association StudiesGenetic LociHEK293 CellsHumansIntronsKidneyKidney DiseasesKidney TransplantationMaleMiceMicrofilament ProteinsPolymorphism, Single NucleotideQuantitative Trait LociRiskSmad3 ProteinTranscription Factor 7-Like 2 ProteinTranscriptional ActivationTransforming Growth Factor beta1ConceptsChronic allograft nephropathyChronic kidney diseaseAllograft fibrosisTGF-β1Development of CANRisk allelesKidney transplant recipientsRenal allograft recipientsGlomerular filtration rateRenal allograft fibrosisTGF-β1 administrationUnilateral ureteric obstructionRenal tubular cellsTranscription factor 7Canonical TGF-β1Cell-specific knockdownAllograft injuryAllograft nephropathyAllograft recipientsTransplant recipientsProspective cohortRenal functionInterstitial fibrosisUreteric obstructionKidney disease